Functional analysis of novel skeletal muscle cell-secreted protein aiming for the establishment of novel therapeutic strategies for sarcopenia
| Project/Area Number |
20K07810
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52010:General internal medicine-related
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
Takemoto Minoru 国際医療福祉大学, 医学部, 主任教授 (60447307)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | サルコペニア / マイオカイン / 自己抗体 / 筋衛星細胞 / 骨格筋 / 高齢者 |
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| Outline of Research at the Start |
本研究の目的はR3hdmlを将来、サルコペニアの新たな治療に結び付けるべく ① 老化モデルマウスや筋萎縮モデルマウスに対するR3hdmlによる治療介入効果とそのメカニズム解析、 ② R3hdmlを実臨床に結びつけるべく、血液中R3hdml濃度を測定しその臨床的意義を明らかにすることである。超高齢社会を迎えている今、健康長寿延伸のためにもサルコペニアのメカニズムの解明と治療法の確立は喫緊の課題である。R3hdml研究を通じて、サルコペニアや筋萎縮で悩む患者の福音としたい。
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| Outline of Final Research Achievements |
Age-related sarcopenia is a risk factor that hinders healthy longevity. Sarcopenia is associated with age-related declining in skeletal muscle regenerative capacity that substantially impairs daily lifestyle activities in the elderly. The proliferation and differentiation of muscle satellite cells are critical for skeletal muscle regeneration. We discovered a new protein called R3h domain containing-like (R3hdml), which is secreted by satellite cells and promotes the proliferation and differentiation of muscle satellite cells. In this study, autoantibodies that inhibit R3hdml action were found to be more prevalent in patients with diabetes, dyslipidemia, fatty liver, obesity, and chronic kidney disease. Inhibiting R3hdml's physiological action may promote sarcopenia through lifestyle-related diseases or by inhibiting the proliferation and differentiation of muscle satellite cells.
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| Academic Significance and Societal Importance of the Research Achievements |
昨年度はR3hdmlに対する自己抗体が慢性腎臓病患者で増加していることを明らかにした。R3hdmlはTGFβ-p38MAPK経路を抑制し、ポドサイトのアポトーシスを抑制する（J Mol Med (Berl). 2021）。今年度の成果によりR3hdml抗体は糖尿病をはじめとした様々な生活習慣病で上昇していることを明らかにした。この上昇したR3hdml抗体は生活習慣病を通じて、もしくは直接、筋衛星細胞の増殖・分化阻害することでサルコペニアを助長する可能性がある。今後、R3hdml抗体に対する介入をすることで、将来のサルコペニア予防のための新たな治療法開発につながる可能性がある。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Utility of atherosclerosis-associated serum antibodies against colony-stimulating factor 2 in predicting the onset of acute ischemic stroke and prognosis of colorectal cancer2023
Author(s)
Li SY, Yoshida Y, Kubota M, 他10名, Ohno M, Nishi E, Kitamura K, Kamitsukasa I, Takizawa H, Sata M, Yamagishi K, Iso H, Sawada N, Tsugane S, Iwase K, Shimada H, Iwadate Y, Hiwasa T.
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Journal Title
Frontiers in Cardiovascular Medicine
Volume: 10
Pages: 1-19
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Time gap between the onset and diagnosis in Werner syndrome: a nationwide survey and the 2020 registry in Japan2020
Author(s)
Koshizaka M, Maezawa Y, Maeda Y, Shoji M, Kato H, Kaneko H, Ishikawa T, Kinoshita D, Kobayashi K, Kawashima J, Sekiguchi A, Motegi SI, Nakagami H, Yamada Y, Tsukamoto S, Taniguchi A, Sugimoto K, Shoda Y, Hashimoto K, Yoshimura T, Suzuki D, Kuzuya M, Takemoto M, Yokote K.
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Journal Title
Aging
Volume: 12
Issue: 24
Pages: 24940-24956
DOI
Related Report
Peer Reviewed / Open Access
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